Plasma membrane electron transport in pancreatic β-cells is mediated in part by NQO1
Plasma membrane electron transport in pancreatic β-cells is mediated in part by NQO1
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DOI：
10.1152/ajpendo.00673.2010
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发表时间：
2011-07-01
影响因子：
5.1
通讯作者：
Heart, Emma
中科院分区：
文献类型：
--
作者：
Gray, Joshua P.;Eisen, Timothy;Heart, Emma
Gray JP，Cline GW，Smith PJ，Heart E.胰腺β细胞中的质膜电子传递部分由NQO 1介导。Am J Physiol Endocrinol Metab 301：E113-E121，2011.首次发表于2011年4月19日; doi：10.1152/ajpendo.00673.2010.-质膜电子传递（PMET）是线粒体电子传递的胞质/质膜类似物，是胞质和质膜氧化还原酶的普遍存在的系统，其氧化胞质NADH和NADPH并将电子传递到细胞外靶标。虽然PMET已被证明在多种细胞类型中发挥重要作用，但没有研究评估其在胰岛素分泌细胞中的功能。在这里，我们证明了在原代胰岛和克隆β细胞中存在强大的PMET活性，如通过减少质膜不可渗透的染料WST-1和铁氰化物所评估的。由于β细胞的代谢功能程度（由胰岛素输出水平反映）在4 - 10 mM葡萄糖之间以葡萄糖依赖性方式增加，因此在这些条件下评价了PMET。PMET活性存在于4 mM葡萄糖下，并在10 mM葡萄糖下进一步刺激。在10 mM葡萄糖下的PMET活性被抑制的黄素蛋白抑制剂diphenyleneiodonium和各种抗氧化剂的应用。胞质NAD（P）H-醌氧化还原酶（NQO 1）的过表达增加了在10 mM葡萄糖存在下的PMET活性，而其抑制剂双香豆素抑制NQO 1则消除了这种活性。线粒体抑制剂鱼藤酮，抗霉素A，氰化钾升高PMET活性。无论葡萄糖水平，PMET活性大大提高了应用aminoxyacetate，苹果酸-天冬氨酸穿梭的抑制剂。我们提出了一个模型的作用PMET作为糖酵解通量的调节剂和β细胞中的代谢机制的重要组成部分。
Gray JP, Eisen T, Cline GW, Smith PJ, Heart E. Plasma membrane electron transport in pancreatic beta-cells is mediated in part by NQO1. Am J Physiol Endocrinol Metab 301: E113-E121, 2011. First published April 19, 2011; doi: 10.1152/ajpendo.00673.2010.-Plasma membrane electron transport (PMET), a cytosolic/plasma membrane analog of mitochondrial electron transport, is a ubiquitous system of cytosolic and plasma membrane oxidoreductases that oxidizes cytosolic NADH and NADPH and passes electrons to extracellular targets. While PMET has been shown to play an important role in a variety of cell types, no studies exist to evaluate its function in insulin-secreting cells. Here we demonstrate the presence of robust PMET activity in primary islets and clonal beta-cells, as assessed by the reduction of the plasma membrane-impermeable dyes WST-1 and ferricyanide. Because the degree of metabolic function of beta-cells (reflected by the level of insulin output) increases in a glucose-dependent manner between 4 and 10 mM glucose, PMET was evaluated under these conditions. PMET activity was present at 4 mM glucose and was further stimulated at 10 mM glucose. PMET activity at 10 mM glucose was inhibited by the application of the flavoprotein inhibitor diphenylene iodonium and various antioxidants. Overexpression of cytosolic NAD(P)H-quinone oxidoreductase (NQO1) increased PMET activity in the presence of 10 mM glucose while inhibition of NQO1 by its inhibitor dicoumarol abolished this activity. Mitochondrial inhibitors rotenone, antimycin A, and potassium cyanide elevated PMET activity. Regardless of glucose levels, PMET activity was greatly enhanced by the application of aminooxyacetate, an inhibitor of the malate-aspartate shuttle. We propose a model for the role of PMET as a regulator of glycolytic flux and an important component of the metabolic machinery in beta-cells.